Johnstone, A; Grigoras, I; Petitet, P; Capitão, LP; Stagg, CJ; (2021) A single, clinically relevant dose of the GABAB agonist baclofen impairs visuomotor learning. The Journal of Physiology , 599 (1) pp. 307-322. 10.1113/JP280378.

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Abstract

KEY POINTS: Baclofen is a GABAB agonist prescribed as a treatment for spasticity in stroke, brain injury and multiple sclerosis patients, who are often undergoing concurrent motor rehabilitation. Decreasing GABAergic inhibition is a key feature of motor learning and so there is a possibility that GABA agonist drugs, like baclofen, could impair these processes, potentially impacting rehabilitation. Here we examined the effect of 10mg baclofen, in 20 young healthy individuals, and found that the drug impaired retention of visuomotor learning with no significant effect on motor sequence learning. Overall baclofen did not alter TMS-measured GABAB inhibition, but the change in GABAB inhibition correlated with aspects of visuomotor learning retention. Further work is needed to investigate whether taking baclofen impacts motor rehabilitation in patients. ABSTRACT: The GABAB agonist baclofen is taken daily as a treatment for spasticity by millions of stroke, brain injury and multiple sclerosis patients, many of whom are also undergoing motor rehabilitation. However, multiple studies suggest that decreases in GABA are a key feature of human motor learning (Floyer-Lea et al. 2006; Stagg et al. 2011; Kolasinski et al. 2018), which raises questions about whether drugs increasing GABAergic activity may impair motor learning and rehabilitation. In this double-blind, placebo-controlled study we investigate whether a single 10mg dose of the GABAB agonist baclofen impaired motor sequence learning and visuomotor learning in 20 young healthy participants of both sexes. Participants trained on visuomotor and sequence learning tasks using their right hand. Transcranial magnetic stimulation (TMS) measures of corticospinal excitability, GABAA (SICI2.5ms ) and GABAB (LICI150ms ) receptor activation were recorded from left M1. Behaviourally, baclofen caused a significant reduction of visuomotor aftereffect (F(1,137.8) = 6.133, p = 0.014) and retention (F(1,130.7) = 4.138, p = 0.044), with no significant changes to sequence learning. There were no overall changes to TMS measured GABAergic inhibition with this low dose of baclofen. This result confirms the causal importance of GABAB inhibition in mediating visuomotor learning and suggests that chronic baclofen use could negatively impact aspects motor rehabilitation.

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